Regiodivergent Hydrosilylation of Polar Enynes to Synthesize Site-Specific Silyl-Substituted Dienes.

Herein, we present catalyst-regulated switchable site-selective hydrosilylation of enynes, which are suitable for a wide range of alkyl and aryl substituted polar enynes and exhibit excellent functional group compatibility. Under the optimized conditions, silyl groups can be precisely installed at various positions of 1,3-dienes. While α- and γ-silylation products were obtained under platinum-catalytic systems, ß-silylation products were delivered with [Cp*RuCl]4 as catalyst. This process lead to the formation of 1,3-dienoates with diverse substitutions, which would pose challenges with other methodologies.

Copper-Catalyzed Regiodivergent and Enantioselective Hydrosilylation of Allenes.

A copper-catalyzed regiodivergent hydrosilylation of a wide range of simple allenes is reported. Linear and branched allylsilanes were formed by judicious choice of solvents. Furthermore, branched allylsilanes were obtained with high enantioselectivity (up to 97% enantiomeric excess) with the aid of a C2-symmetric bisphosphine ligand in the unprecedented asymmetric allene hydrosilylation.

Dienylation of N-benzoylhydrazones with CF3-substituted homoallenylboronates in water.

A convenient method for the dienylation of N-benzoylhydrazones in water has been developed. This protocol expanded the synthetic application of functionalized homoallenylboronates to provide the useful 2-aminomethyl-1,3-diene derivatives with high efficiency (up to 99% yield) and stereoselectivity without using any catalyst, additive or inert atmosphere. Furthermore, the transformation of a 2-aminomethyl-1,3-diene derivative to synthesize a functionalized pyrrolidine derivative was also explored.

Palladium-Catalyzed Cascade Intramolecular Cyclization and Allylation of Enynoates with Allylic Alcohols.

A Pd(II)-catalyzed mild and highly regioselective 6- endo cyclization/allylation reaction of enynoates with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert C-C double bond of allylic alcohol through cross-coupling reaction and lead to the formation of allyl pyrone via ß-OH elimination. This cascade cross-coupling reaction represents a direct and atom economic methodology for the construction of novel allyl pyrones in moderate to good yields.

Palladium-Catalyzed Cycloaromatization/Alkylation of o-(Alkynyl)styrenes.

A Pd(II)-catalyzed mild and highly regioselective 6-endo cyclization/alkylation reaction of o-(alkynyl)styrenes with simple allylic alcohols has been developed. Under mild reaction conditions, the vinyl palladium species generated in situ after cyclization could insert a C-C double bond of allylic alcohol through a cross-coupling reaction and led to the formation of (alkyl)naphthalenes. This cascade cross-coupling reaction represents a direct and atom economic method for the construction of functionalized naphthalene derivatives in moderate to good yields.

Copper-catalyzed regiodivergent 1,4- and 1,6-conjugate silyl addition to diendioates: access to functionalized allylsilanes.

A copper-catalyzed regioselective 1,4- and 1,6-conjugate addition of a silyl reagent to diendioates was established. Various 1,4- and 1,6-protosilylation products were obtained in good yields and with high regioselectivity via tuning the ligands used in the reactions. This protocol has provided a simple and efficient method for the synthesis of multisubstituted functionalized allylsilanes.

Copper-Catalyzed Asymmetric Silylation of Propargyl Dichlorides: Access to Enantioenriched Functionalized Allenylsilanes.

A copper-catalyzed silylation of propargyl dichlorides was developed to access chloro-substituted allenylsilanes under mild reaction conditions. Moreover, enantioenriched chloro-substituted allenylsilanes can be synthesized in moderate to high yields and good enantioselectivities with this protocol.

Palladium-Catalyzed One-Pot Highly Regioselective 6- Endo Cyclization and Alkylation of Enynoates: Synthesis of 2-Alkanone Pyrones.

The Pd(II)-catalyzed one-pot tandem cyclization/alkylation reactions of enynoates with allylic alcohols have been demonstrated. In this reaction, an innovative protocol proceeded well through Pd-catalyzed intramolecular selective 6- endo cyclization, insertion of allylic alcohols into the Pd-C bond of vinylpalladium species generated in situ, and ß-hydrogen elimination processes. This conversion provides a convenient and efficient methodology for the synthesis of 2-alkanone pyrones in moderate to good yields.

Palladium-Catalyzed Regioselective Olefination of O-Acetyl Cyanohydrins.

A practical palladium-catalyzed ortho-olefination of O-acetyl cyanohydrins assisted by synergetic directing groups has been developed. Thus, a range of olefinated O-acetyl cyanohydrins were synthesized in moderate to good yields. The reaction occurs efficiently with high regioselectivity and with a satisfactory tolerance of functional groups.

Macrolide Synthesis through Intramolecular Oxidative Cross-Coupling of Alkenes.

A RhIII -catalyzed intramolecular oxidative cross-coupling between double bonds for the synthesis of macrolides is described. Under the optimized reaction conditions, macrocycles containing a diene moiety can be formed in reasonable yields and with excellent chemo- and stereoselectivity. This method provides an efficient approach to synthesize macrocyclic compounds containing a 1,3-conjugated diene structure.

Chelation versus Non-Chelation Control in the Stereoselective Alkenyl sp2 C-H Bond Functionalization Reaction.

A hydroxy group chelation-assisted stereospecific oxidative cross-coupling reaction between alkenes was developed under mild reaction conditions. In the presence of palladium catalyst, the alkenes tethered with hydroxy functionality can couple efficiently with electron-deficient alkenes to form the corresponding multi-substituted olefin products. The hydroxy group on the substrate could play dual roles in reaction, acting as the directing group for alkenyl C-H bond activation and controlling the stereoselectivity of the products.

Pd-catalyzed intramolecular C-N bond cleavage, 1,4-migration, sp3 C-H activation, and Heck reaction: four controllable diverse pathways depending on the judicious choice of the base and ligand.

Diverse and controllable pathways induced by palladium-catalyzed intramolecular Heck reaction of N-vinylacetamides for the synthesis of nitrogen-containing products in reasonable to high yields via tuning the phosphine ligands and bases are reported. Domino reactions including unique ß-N-Pd elimination, 1,4-Pd migration, or direct acyl C-H bond functionalization were found to be involved forming different products, respectively. Given the ability of using the same starting material to generate diverse products via completely different chemoselective processes, these current methodologies offer straightforward access to valuable nitrogen-containing products under mild reaction conditions as well as inspire the discovery of novel reactions.

Synthesis of Highly Substituted Racemic and Enantioenriched Allenylsilanes via Copper-Catalyzed Hydrosilylation of (Z)-2-Alken-4-ynoates with Silylboronate.

Copper-catalyzed highly efficient hydrosilylation reaction of enynoates was developed. Under simple reaction conditions, various di-, tri-, and tetrasubstituted racemic allene products could be obtained in high yields. The asymmetric 1,6-addition of silyl group to the (Z)-2-alken-4-ynoates could be achieved under mild reaction conditions to afford the silyl-substituted enantioenriched chiral allene products in good yields and with high enantioselectivities.

Stereo- and chemoselective cross-coupling between two electron-deficient acrylates: an efficient route to (Z,E)-muconate derivatives.

A Ru-catalyzed direct oxidative cross-coupling reaction of acrylates was developed. It offers a straightforward and atom-economical protocol for the synthesis of functionalized (Z,E)-muconate derivatives in moderate to good yields with good stereo- and chemoselectivities. The conjugated muconates bearing differentiable terminal functionality can be selectively transformed into versatile synthetic intermediates widely used in organic synthesis.

Cu-Catalyzed Regioselective Silylation of Chloro-Substituted Allenyl-Bdan.

A copper-catalyzed efficient regioselective silylation reaction of chloro-substituted allenyl-Bdan was developed. Under mild reaction conditions, allenyl and propargyl silane compounds can be selectively obtained in moderate to high yields by adjusting the bases and solvents used in the reactions. This study offers direct and efficient methods for synthesizing multifunctionalized allenyl and propargyl silane compounds from the same initial material of chloro-substituted allenyl-Bdan.

Synthesis and Transformation of Bis(silyl)-Substituted Conjugated Vinylallene Compounds.

We develop a copper-catalyzed disilylation of polysubstituted pent-1-en-4-yn-3-yl acetate derivatives, which in one pot furnishes the bis(silyl)-substituted vinylallenes in moderate yields under mild reaction conditions. The reaction shows broad substrate scope and single stereoselectivity. Besides, we develop a method to decrease the electrocyclization temperature of vinylallenes for the synthesis of methylenecyclobutenes by installing bis(silyl) substituents. And the effect of a silyl substituent on electrocyclization of vinylallenes was studied via DFT computation. The synthetic method features broad substrate scope and excellent stereoselectivity.

Copper-Catalyzed Enantioselective Desymmetric Protosilylation of Prochiral Diynes: Access to Optically Functionalized Tertiary Alcohols.

In this protocol, a copper-catalyzed desymmetric protosilylation of prochiral diynes was developed. The corresponding products were obtained in moderate to high yields and enantiomeric ratios. This approach provides a simple method for synthesizing functionalized chiral tertiary alcohols in the presence of a chiral pyridine-bisimidazoline (Pybim) ligand.

Copper-Catalyzed Regio- and Stereoselective Three-Component Coupling of Allenyl Ethers with gem-Dichlorocyclobutenones and B2pin2.

The three-component coupling method for regio- and stereoselective difunctionalization of allenes with allenyl ethers, bis(pinacolato)diboron, and gem-dichlorocyclobutenones as electrophiles was reported, yielding a variety of highly functionalized cyclobutenone products tethering with an alkenylborate fragment. The polysubstituted cyclobutenone products also underwent diverse transformations.

Copper-Catalyzed Borylation and Silylation of Dichlorocyclobutenones.

We report copper-catalyzed borylation and silylation of dichlorocyclobutenones, which furnish the boron-substituted and silicon-substituted polyfunctionalized cyclobutenones in high yields. The reactions proceed under mild reaction conditions, show broad substrate scope, and display high chemoselectivity. In addition, a series of transformations of the corresponding products has been realized.

Regio- and enantioselective CuH-catalyzed 1,2- and 1,4-hydrosilylation of 1,3-enynes.

We report a copper-catalyzed ligand-controlled selective 1,2- and 1,4-hydrosilylation of 1,3-enynes, which furnishes enantiomerically enriched propargyl- and 1,2-allenylsilane products in high yields with excellent enantioselectivities (up to 99% ee). This reaction proceeds under mild conditions, shows broad substrate scope for both 1,3-enynes and trihydrosilanes, and displays excellent regioselectivities. Mechanistic studies based on deuterium-labeling reactions and density functional theory (DFT) calculations suggest that allenylcopper is the dominant reactive intermediate under both 1,2- and 1,4-hydrosilylation conditions, and it undergoes metathesis with silanes via selective four-membered or six-membered transition state, depending on the nature of the ligand. The weak interactions between the ligands and the reacting partners are found to be the key controlling factor for the observed regioselectivity switch. The origin of high enantiocontrol in the 1,4-hydrosilylation is also revealed by high level DLPNO-CCSD(T) calculations.